alpha-thrombin stimulates expression of macrophage migration inhibitory factor in skin fibroblasts

Macrophage migration inhibitory factor (MIF) is induced by various stimuli such as wounds and infection and regulates inflammatory and immunological r esponses, To date, we have found increased expression of MIF during the wou nd healing process in rat skin. Immunohistochemical analysis demonstrated e nhanced expression of MIF in wound skin lesions. On the other hand, alpha-t hrombin, a multifunctional serine protease, plays an important role in woun d healing with regard to induction of inflammatory cytokines such as interl eukin-6 (IL-6), Accordingly, we examined the effect of alpha-thrombin on MI F production in human skin fibroblasts, alpha-Thrombin significantly stimul ated MIF secretion into culture medium of fibroblasts quantitated by an enz yme-linked immunosorbent assay (ELISA), Consistent with this, we observed t he upregulation of MIF mRNA in response to alpha-thrombin by Northern blot analysis, Taken together, these results suggest that MIF produced by fibrob lasts in response to alpha-thrombin plays an important regulatory role in w ound repair.